Low Dose Ribavirin for Treatment of Hepatitis C Virus Infected Thalassemia Major Patients; New Indications for Combination Therapy

Abstract

Background Treatment guidelines contraindicate ribavirin for treatment of hepatitis C virus (HCV) infection in thalassemia major patients. Nevertheless, the current evidence suggests that ribavirin might be tolerated by these patients. Objectives Despite this evidence, low dose ribavirin combination therapy has not been compared with peginterferon monotherapy in these patients so far. Patients and Methods Two hundred eighty thalassemia patients with detectable HCV-RNA PCR (≥ 50 IU/mL) and liver histology consistent with chronic HCV infection were self-assigned to receive peginterferon alfa-2a (n = 81) monotherapy or its combination therapy with ribavirin, 600-800 mg QD, according to hemoglobin levels (n = 199). Treatment experienced patients were eligible for this study. Results Sustained virological response (SVR) was significantly higher in patients who received ribavirin (51 % vs. 38 % P = 0.02). In multivariate regression, OR of ribavirin for prediction of SVR was 2.2 (95 % CI 1.24-3.91). The SVR was significantly higher in the ribavirin group in subgroups of patients with more than 24 years of age, elevated ALT, ferritin < 2006 ng/mL, previous treatment failure, genotype 1, positive history of splenectomy, fibrosis score of 0-4 HAI and viral load < 600,000 IU/mL. Treatment discontinuations due to the safety concerns were comparable between the treatment groups (6.5 and 8 %). Furthermore, transfusion intervals were almost halved in patients who received low dose ribavirin. Conclusions According to the present study, adult thalassemia patients with HCV infection can be treated successfully with low dose ribavirin. Hence, we strongly advise combination therapy in thalassemia patients with aforementioned clinical characteristics. Moreover, ribavirin does not seem to be beneficial in thalassemia patients below 18 years of age.

Consensus Statement of HCV Task Force of the Indian National Association for Study of the Liver (INASL). Part II: INASL Recommendations for Management of HCV in India

“…Neutropenia may be managed with growth factors but use of erythropoietin is not recommended. 107 Tabatabaei et al 108 have described that combination therapy with RBV when tailored according to Hb (800 mg when Hb-10 g, 600 mg when Hb < 10 g) to have significantly higher SVR rates when compared to monotherapy.…”

Efficacy of Prolonged Treatment With Pegylated Interferon (Peg-IFN) and Ribavirin in Thalassemic Patients With Hepatitis C Who Relapsed After Previous Peg-IFN-Based Therapy

“…Treatment of chronic HCV infection in thalassemic patients is complicated by hepatic siderosis and ribavirin (RBV) dose reduction caused by RBV-induced anemia. Clinical trials investigating the efficacy of pegylated interferon (Peg-IFN) and RBV in HCV-infected thalassemic patients demonstrated overall sustained virological response (SVR) rates ranging from 50% to 62% ( 7 , 8 ). Moreover, the iron overload worsens the outcome of liver disease following multiple transfusion, often reducing the chance of achieving SVR.…”

Burden of Hepatitis C on Patients with Thalassemia

“…Control of Hepatitis C virus (HCV) infection has been amongst our priorities in Iran and most individuals are evaluated for HCV infection and treated as well (2,3). However, we found some points that need further clarification.…”